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Full-Text Articles in Life Sciences
Anti-Cancer Activity Of An Acid-Labile N-Alkylisatin Conjugate Targeting The Transferrin Receptor, Vineesh Indira Chandran, Lidia Matesic, Julie Locke, Danielle Skropeta, Marie Ranson, Kara Vine
Anti-Cancer Activity Of An Acid-Labile N-Alkylisatin Conjugate Targeting The Transferrin Receptor, Vineesh Indira Chandran, Lidia Matesic, Julie Locke, Danielle Skropeta, Marie Ranson, Kara Vine
Danielle Skropeta
We have previously reported a series of pH-sensitive imine-linked N-alkylisatin prodrugs that are stable at pH 7.4, but readily cleaved at pH 4.5. Herein, one of the most potent prodrugs, 5,7-dibromo-N-(pmethoxybenzyl) isatin (NAI), was functionalized with a para-phenylpropionic acid linker, and the resulting NAI–imine prodrug conjugated to transferrin (Tf) to form a NAI–imine–Tf conjugate. Cytotoxicity assays revealed the conjugate was equipotent to the free drug against MCF-7 breast cancer cells, with clear selectivity patterns based on TfR levels. These results suggest that this novel isatin-based cytotoxin conjugated to a tumor targeting protein via an acid-labile linker warrants further preclinical testing.
The Effect Of Individual N-Glycans On Enzyme Activity, Danielle Skropeta
The Effect Of Individual N-Glycans On Enzyme Activity, Danielle Skropeta
Danielle Skropeta
No abstract provided.
Domino Pericyclic Reactions Of Acyclic Conjugated (E,Z,E,E)-Tetraenes, Danielle Skropeta, Rodney Rickards
Domino Pericyclic Reactions Of Acyclic Conjugated (E,Z,E,E)-Tetraenes, Danielle Skropeta, Rodney Rickards
Danielle Skropeta
No abstract provided.
N-Phenethyl And N-Naphthylmethyl Isatins And Analogues As In Vitro Cytotoxic Agents, John Bremner, Stephen Pyne, Marie Ranson, Danielle Skropeta, Julie Locke, Lidia Matesic, Kara Perrow
N-Phenethyl And N-Naphthylmethyl Isatins And Analogues As In Vitro Cytotoxic Agents, John Bremner, Stephen Pyne, Marie Ranson, Danielle Skropeta, Julie Locke, Lidia Matesic, Kara Perrow
Danielle Skropeta
Arange of N-phenethyl,N-phenacyl, and N-(1- and 2-naphthylmethyl) derivatives of 5,7-dibromoisatin 2 were prepared byN-alkylation reactions. Their activity against human monocyte-like histiocytic lymphoma (U937), leukemia (Jurkat), and breast carcinoma (MDA-MB-231) cell lines was assessed. The results allowed further development of structureactivity relationships. The compound 5,7-dibromo-N-(1-naphthylmethyl)-1H-indole-2,3-dione 5a was the most potent against U937 cells with an IC50 value of 0.19 microM.
Complete Assignment Of The 1h And 13c Nmr Spectra Of Antimicrobial 4-Arylamino- 3-Nitrocoumarin Derivatives, Vidoslav Dekic, Niko Radulovic, Rastko Vukicevic, Biljana Dekic, Danielle Skropeta, Radosav Palic
Complete Assignment Of The 1h And 13c Nmr Spectra Of Antimicrobial 4-Arylamino- 3-Nitrocoumarin Derivatives, Vidoslav Dekic, Niko Radulovic, Rastko Vukicevic, Biljana Dekic, Danielle Skropeta, Radosav Palic
Danielle Skropeta
No abstract provided.
Synthesis And Hydrolytic Evaluation Of Acid-Labile Imine-Linked Cytoxic Isatin Model Systems, Lidia Matesic, Julie Locke, Kara Perrow, Marie Ranson, John Bremner, Danielle Skropeta
Synthesis And Hydrolytic Evaluation Of Acid-Labile Imine-Linked Cytoxic Isatin Model Systems, Lidia Matesic, Julie Locke, Kara Perrow, Marie Ranson, John Bremner, Danielle Skropeta
Danielle Skropeta
In this study a series of isatin-based, pH-sensitive aryl imine derivatives with differing aromatic substituents and substitution patterns were synthesised and their acid-catalysed hydrolysis evaluated. These derivatives were functionalised at the C3 carbonyl group of a potent N-substituted isatin cytotoxin and were stable at physiological pH but readily cleaved at pH 4.5. Observed rates of hydrolysis for the embedded imine-acid moiety were in the order para-phenylpropionic acid>phenylacetic acid (para>meta)>benzoic acid (meta>para). The ability to fine-tune hydrolysis rates in this way has potential implications for optimising imine linked, tumour targeting cytotoxin-protein conjugates
N-Glycolisation Regulates Endothelial Lipase-Mediated Phospholipid Hydrolysis In Apoe- And Apoa-I-Containing High Density Lipoproteins, Danielle Skropeta, Daniel Rader, Weijun Jin, Monica Mcmahon, Kate Shearston, Philip Barter, Kristine Mcgrath, Kerry-Anne Rye, Chatri Settasatian, Daniela Caiazza
N-Glycolisation Regulates Endothelial Lipase-Mediated Phospholipid Hydrolysis In Apoe- And Apoa-I-Containing High Density Lipoproteins, Danielle Skropeta, Daniel Rader, Weijun Jin, Monica Mcmahon, Kate Shearston, Philip Barter, Kristine Mcgrath, Kerry-Anne Rye, Chatri Settasatian, Daniela Caiazza
Danielle Skropeta
No abstract provided.
Cytotoxic And Anticancer Activities Of Isatin And Its Derivatives: A Comprehensive Review From 2000-2008, Marie Ranson, Danielle Skropeta, Julie Locke, Lidia Matesic, Kara Perrow
Cytotoxic And Anticancer Activities Of Isatin And Its Derivatives: A Comprehensive Review From 2000-2008, Marie Ranson, Danielle Skropeta, Julie Locke, Lidia Matesic, Kara Perrow
Danielle Skropeta
No abstract provided.
Chemotaxonomy Of The Peppergrass Lepidium Coronopus (L.) Al-Shehbaz (Syn. Coronopus Squamatus) Based On Its Volatile Glucosinolate Autolysis Products, Niko Radulovic, Bojan Zlatkovic, Danielle Skropeta, Radosav Palic´
Chemotaxonomy Of The Peppergrass Lepidium Coronopus (L.) Al-Shehbaz (Syn. Coronopus Squamatus) Based On Its Volatile Glucosinolate Autolysis Products, Niko Radulovic, Bojan Zlatkovic, Danielle Skropeta, Radosav Palic´
Danielle Skropeta
The genus Lepidium comprises approximately 175 different plant species commonly referred to as peppergrasses or pepperworts ( Al-Shehbaz, 1997 and Mummenhoff et al., 2001), which occur worldwide apart from the polar regions where they are considered rare in the Arctic and are absent from Antarctica. Lepidium is a comparatively large genus belonging to the mustard family Brassicaceae. Lepidium coronopus (L.) Al-Shehbaz, a representative of the genus, is a herbaceous annual to biennial plant that belongs to the tribe Lepidieae and has previously been described by the following synonymous species: Coronopus squamatus (Forsskal) Ascherson; C. squamatus subsp. conradi (Muschler) Maire; C. …
Apolipoprotein J And Leptin Levels In Patients With Coronary Heart Disease, Mark Wilson, Dimitri Mikhailidis, Maria Poulakou, Christos Tsigris, Despina Perrea, Kosmas Paraskevas, Dimitrios Iliopoulos
Apolipoprotein J And Leptin Levels In Patients With Coronary Heart Disease, Mark Wilson, Dimitri Mikhailidis, Maria Poulakou, Christos Tsigris, Despina Perrea, Kosmas Paraskevas, Dimitrios Iliopoulos
Mark R Wilson
No abstract provided.
Ozone-Induced Dissociation On A Modified Tandem Linear Ion-Trap: Observations Of Different Reactivity For Isomeric Lipids, Berwyck Poad, Huong Pham, Michael Thomas, Jessica Hughes, J Campbell, Todd Mitchell, Stephen Blanksby
Ozone-Induced Dissociation On A Modified Tandem Linear Ion-Trap: Observations Of Different Reactivity For Isomeric Lipids, Berwyck Poad, Huong Pham, Michael Thomas, Jessica Hughes, J Campbell, Todd Mitchell, Stephen Blanksby
Berwyck L. J. Poad
Ozone-induced dissociation (OzID) exploits the gas-phase reaction between mass-selected lipid ions and ozone vapor to determine the position(s) of unsaturation. In this contribution, we describe the modification of a tandem linear ion-trap mass spectrometer specifically for OzID analyses wherein ozone vapor is supplied to the collision cell. This instrumental configuration provides spatial separation between mass-selection, the ozonolysis reaction, and mass-analysis steps in the OzID process and thus delivers significant enhancements in speed and sensitivity (ca. 30-fold). These improvements allow spectra revealing the double-bond position(s) within unsaturated lipids to be acquired within 1 s: significantly enhancing the utility of OzID in …
Synthesis Of Functionalised 2-Aryl-5-Nitro-1h-Indoles And Their Activity As Bacterial Nora Efflux Pump Inhibitors, John Bremner, Siritron Samosorn, Anthony Ball, Kim Lewis
Synthesis Of Functionalised 2-Aryl-5-Nitro-1h-Indoles And Their Activity As Bacterial Nora Efflux Pump Inhibitors, John Bremner, Siritron Samosorn, Anthony Ball, Kim Lewis
Kim Lewis
No abstract provided.
Conjugating Berberine To A Multidrug Resistance Pump Inhibitor Creates An Effective Antimicrobial, John Bremner, Siritron Samosorn, Anthony Ball, Gabriele Casadei, Terence Moy, Frederik Ausubel, Kim Lewis
Conjugating Berberine To A Multidrug Resistance Pump Inhibitor Creates An Effective Antimicrobial, John Bremner, Siritron Samosorn, Anthony Ball, Gabriele Casadei, Terence Moy, Frederik Ausubel, Kim Lewis
Kim Lewis
No abstract provided.
Structure-Activity Relationships Of 2-Aryl-1h-Indole Inhibitors Of The Nora Efflux Pump In Staphylococcus Aureus, John Bremner, Michael Kelso, Joseph Ambrus, Kim Lewis, Anthony Ball, Gabriele Casadei
Structure-Activity Relationships Of 2-Aryl-1h-Indole Inhibitors Of The Nora Efflux Pump In Staphylococcus Aureus, John Bremner, Michael Kelso, Joseph Ambrus, Kim Lewis, Anthony Ball, Gabriele Casadei
Kim Lewis
The synthesis of 22 2-aryl-1H-indoles, including 12 new compounds, has been achieved via Pd- or Rh-mediated methodologies, or selective electrophilic substitution. All three methods were based on elaborations from simple indole precursors. SAR studies on these indoles and 2-phenyl-1H-indole in Staphylococcus aureus as NorA efflux pump inhibitors indicated 5-nitro-2-(3-methoxycarbonyl)phenyl-1H-indole was a slightly more potent inhibitor than the lead INF55. A promising new antibacterial lead compound against S. aureus (2-phenyl-1H-indol-5-yl)-methanol, was also found.
Combining Mbr And Nf/Ro Membrane Filtration For The Removal Of Trace Organics In Indirect Potable Water Reuse Applications, William Price, Nichanan Tadkaew, Long Nghiem, Stuart Khan, Abdulhakeem Alturki, James Mcdonald
Combining Mbr And Nf/Ro Membrane Filtration For The Removal Of Trace Organics In Indirect Potable Water Reuse Applications, William Price, Nichanan Tadkaew, Long Nghiem, Stuart Khan, Abdulhakeem Alturki, James Mcdonald
Long D Nghiem
The aim of this study was to demonstrate the complementarities of combining membrane bioreactor (MBR) treatment with nanofiltration (NF) or reverse osmosis (RO) membrane filtration for the removal of trace organic contaminants for potential indirect potable water recycling applications. Four commercially available NF/RO membranes, namely NF270, NF90, BW30 and ESPA2, were selected for this investigation. Challenge tests were conducted with 40 trace organic compounds at concentrations of approximately 2 ng/L in initial wastewater solutions using a laboratory scaleMBRsystem and a cross-flow NF/RO rig. The results suggest that the MBR system effectively removes hydrophobic and biodegradable trace organic compounds. The adsorption …
Nmr Spectroscopy Of 14-3-3zeta Reveals A Flexible C-Terminal Extension: Differentiation Of The Chaperone And Phosphoserine-Binding Activities Of 14-3-3zeta, H Fu, Danielle Williams, Heath Ecroyd, John Carver, Lixin Zhang, Huanqin Dai, Joanna Woodcock, K Goodwin
Nmr Spectroscopy Of 14-3-3zeta Reveals A Flexible C-Terminal Extension: Differentiation Of The Chaperone And Phosphoserine-Binding Activities Of 14-3-3zeta, H Fu, Danielle Williams, Heath Ecroyd, John Carver, Lixin Zhang, Huanqin Dai, Joanna Woodcock, K Goodwin
Heath Ecroyd
Intracellular 14-3-3 proteins bind to many proteins, via a specific phosphoserine motif, regulating diverse cellular tasks including cell signalling and disease progression. The 14-3-3 isoform is a molecular chaperone, preventing the stressinduced aggregation of target proteins in a manner comparable with that of the unrelated sHsps (small heat-shock proteins). 1H-NMR spectroscopy revealed the presence of a flexible and unstructured C-terminal extension, 12 amino acids in length, which protrudes from the domain core of 14-3-3 and is similar in structure and length to the C-terminal extension of mammalian sHsps. The extension stabilizes 14-3-3, but has no direct role in chaperone action. …
Enhanced Molecular Chaperone Activity Of The Small Heat-Shock Protein Alphab-Cystallin Following Covalent Immobilization Onto A Solid-Phase Support, V Bellotti, Heath Ecroyd, J Carver, H J Griesser, B Thierry, J G Shapter, S S Griesser, S Giorgetti, M R Nussio, J A Gerrard, J Garvey
Enhanced Molecular Chaperone Activity Of The Small Heat-Shock Protein Alphab-Cystallin Following Covalent Immobilization Onto A Solid-Phase Support, V Bellotti, Heath Ecroyd, J Carver, H J Griesser, B Thierry, J G Shapter, S S Griesser, S Giorgetti, M R Nussio, J A Gerrard, J Garvey
Heath Ecroyd
The well-characterized small heat-shock protein, alphaB-crystallin, acts as a molecular chaperone by interacting with unfolding proteins to prevent their aggregation and precipitation. Structural perturbation (e.g., partial unfolding) enhances the in vitro chaperone activity of alphaB-crystallin. Proteins often undergo structural perturbations at the surface of a synthetic material, which may alter their biological activity. This study investigated the activity of alphaB-crystallin when covalently bound to a support surface; alphaB-crystallin was immobilized onto a range of solid material surfaces, and its characteristics and chaperone activity were assessed. Immobilization was achieved via a plasma-deposited thin polymeric interlayer containing aldehyde surface groups and reductive …
3-Hydroxykynurenine Oxidizes Alpha-Crystallin: Potential Role In Cataractogenesis, Roger Truscott, Andrew Aquilina, Peter Hains, Anastasia Korlimbinis
3-Hydroxykynurenine Oxidizes Alpha-Crystallin: Potential Role In Cataractogenesis, Roger Truscott, Andrew Aquilina, Peter Hains, Anastasia Korlimbinis
J. A. Aquilina
No abstract provided.
Truncation, Cross-Linking And Interaction Of Crystallins And Intermediate Filament Proteins In The Aging Human Lens, Roger Truscott, Jason Mcarthur, Andrew Aquilina, Shi-Ping (Jim) Su
Truncation, Cross-Linking And Interaction Of Crystallins And Intermediate Filament Proteins In The Aging Human Lens, Roger Truscott, Jason Mcarthur, Andrew Aquilina, Shi-Ping (Jim) Su
J. A. Aquilina
The optical properties of the lens are dependent upon the integrity of proteins within the fiber cells. During aging, crystallins, the major intra-cellular structural proteins of the lens, aggregate and become water-insoluble. Modifications to crystallins and the lens intermediate filaments have been implicated in this phenomenon. In this study, we examined changes to, and interactions between, human lens crystallins and intermediate filament proteins in lenses from a variety of age groups (0-86 years). Among the lens-specific intermediate filament proteins, filensin was extensively cleaved in all postnatal lenses, with truncated products of various sizes being found in both the lens cortical …
Chemical Cross-Linking Of The Chloroplast Localized Small Heat-Shock Protein, Hsp21, And The Model Substrate Citrate Synthase, Emma Ahrman, W Lambert, Andrew Aquilina, C V Robinson, Cs Emanuelsson
Chemical Cross-Linking Of The Chloroplast Localized Small Heat-Shock Protein, Hsp21, And The Model Substrate Citrate Synthase, Emma Ahrman, W Lambert, Andrew Aquilina, C V Robinson, Cs Emanuelsson
J. A. Aquilina
The molecular mechanism whereby the small heat-shock protein (sHsp) chaperones interact with and prevent aggregation of other proteins is not fully understood. We have characterized the sHsp-substrate protein interaction at normal and increased temperatures utilizing a model substrate protein, citrate synthase (CS), widely used in chaperone assays, and a dodecameric plant sHsp, Hsp21, by chemical cross-linking with 3,3'-Dithiobis[sulfosuccinimidylpropionate] (DTSSP) and mass spectrometric peptide mapping. In the absence of CS, the cross-linker captured Hsp21 in dodecameric form, even at increased temperature (47 degrees C). In the presence of equimolar amounts of CS, no Hsp21 dodecamer was captured, indicating a substrate-induced Hsp21 …
Effects Of Glycosylation On The Structure And Function Of The Extracellular Chaperone Clusterin, Elise Stewart, Andrew Aquilina, Simon B Easterbrook-Smith, D Murphy-Durland, C Jacobsen, S Moestrup, Mark Wilson
Effects Of Glycosylation On The Structure And Function Of The Extracellular Chaperone Clusterin, Elise Stewart, Andrew Aquilina, Simon B Easterbrook-Smith, D Murphy-Durland, C Jacobsen, S Moestrup, Mark Wilson
J. A. Aquilina
Clusterin is the first well characterized, constitutively secreted extracellular chaperone that binds to exposed regions of hydrophobicity on non-native proteins. It may help control the folding state of extracellular proteins by targeting them for receptor-mediated endocytosis and intracellular lysosomal degradation. A notable feature of secreted clusterin is its heavy glycosylation. Although carbohydrate comprises approximately 20−25% of the total mass of the mature molecule, its function is unknown. Results from the current study demonstrate that deglycosylation of human serum clusterin had little effect on its overall secondary structure content but produced a small increase in solvent-exposed hydrophobicity and enhanced the propensity …
Protein-Bound And Free Uv Filters In Cataract Lenses. The Concentration Of Uv Filters Is Much Lower Than In Normal Lenses, Roger Truscott, Andrew Aquilina, Anastasia Korlimbinis
Protein-Bound And Free Uv Filters In Cataract Lenses. The Concentration Of Uv Filters Is Much Lower Than In Normal Lenses, Roger Truscott, Andrew Aquilina, Anastasia Korlimbinis
J. A. Aquilina
In human cataract lenses the UV filters, 3-hydroxykynurenine glucoside (3OHKG) and kynurenine (Kyn) were found to be covalently bound to proteins and the levels in the nucleus were much higher than in the cortex. The levels of the bound UV filters in cataract nuclei were much lower than those in age-matched normal lenses. 3-Hydroxykynurenine could not be detected in cataract lenses. As with normal lenses, protein-bound 3OHKG in cataract lenses was found at the highest levels followed by Kyn. Free UV filter concentrations were also markedly reduced in cataract lenses. This feature may well contribute to the lower protein-bound levels; …
Protein-Bound Uv Filters In Normal Human Lenses: The Concentration Of Bound Uv Filters Equals That Of Free Uv Filters In The Centre Of Older Lenses, Roger Truscott, Andrew Aquilina, Anastasia Korlimbinis
Protein-Bound Uv Filters In Normal Human Lenses: The Concentration Of Bound Uv Filters Equals That Of Free Uv Filters In The Centre Of Older Lenses, Roger Truscott, Andrew Aquilina, Anastasia Korlimbinis
J. A. Aquilina
No abstract provided.
Amyloid Fibril Formation By Bovine Milk Alpha(S2)-Casein Occurs Under Physiological Conditions Yet Is Prevented By Its Natural Counterpart, Alpha(S1)-Casein, David Thorn, Heath Ecroyd, M Sunde, Stephen Poon, John Carver
Amyloid Fibril Formation By Bovine Milk Alpha(S2)-Casein Occurs Under Physiological Conditions Yet Is Prevented By Its Natural Counterpart, Alpha(S1)-Casein, David Thorn, Heath Ecroyd, M Sunde, Stephen Poon, John Carver
Heath Ecroyd
The calcified proteinaceous deposits, or corpora amylacea, of bovine mammary tissue often comprise a network of amyloid fibrils, the origins of which have not been fully elucidated. Here, we demonstrate by transmission electron microscopy, dye binding assays, and X-ray fiber diffraction that bovine milk alpha(s2)-casein, a protein synthesized and secreted by mammary epithelial cells, readily forms fibrils in vitro. As a component of whole alpha(s)-casein, alpha(s2)-casein was separated from alpha(s1)-casein under nonreducing conditions via cation-exchange chromatography. Upon incubation at neutral pH and 37 degrees C, the spherical particles typical of alpha(s2)-casein rapidly converted to twisted, ribbon-like fibrils similar to 12 …
Protective Interactions Of Dairy Peptides With Fibril Structures And Relevance To Alzheimer's Disease, Louise Bennett, Williams Roderick, Heath Ecroyd, Yanqin Liu, Sunanda Sudharmarajan, John Carver
Protective Interactions Of Dairy Peptides With Fibril Structures And Relevance To Alzheimer's Disease, Louise Bennett, Williams Roderick, Heath Ecroyd, Yanqin Liu, Sunanda Sudharmarajan, John Carver
Heath Ecroyd
Selected dairy caseins have been shown to have capacity for chaperone-like regulation of folding pathways of other caseins, specifically in preventing development of fibrillar aggregates of beta sheet structure. An assay based on fibril formation by reduced and carboxymethylated-kappa casein (RCM-kCn) was thus used to screen for anti-fibril activity among a selection of dairy protein hydrolysates, in order to discover peptides with possible anti-fibril, chaperone activity. From the selection of eight dairy hydrolysates based on different dairy protein fractions, two of the hydrolysates of whey protein exhibited superior anti-fibril bioactivity against RCM-kCn and amyloid beta (Aβ), the peptide associated with …